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Catalytic Site Atlas

CSA LITERATURE entry for 1ssx

E.C. namealpha-lytic endopeptidase
SpeciesLysobacter enzymogenes ()
E.C. Number (IntEnz) 3.4.21.12
CSA Homologues of 1ssxThere are 254 Homologs
CSA Entries With UniProtID P00778
CSA Entries With EC Number 3.4.21.12
PDBe Entry 1ssx
PDBSum Entry 1ssx
MACiE Entry 1ssx

Literature Report

IntroductionAlpha-lytic protease is a bacterial homolog of the chymotrypsin family of serine proteases. The role of this unusually stable extracellular enzyme is to lyse microorganisms and proteolyse their contents to provide nutrients for the host bacterium. The enzyme preferentially cleaves Ala-|-Xaa, Val-|-Xaa in bacterial cell walls, elastin and other proteins.
MechansimAlpha-lytic protease employs a classic Ser-His-Asp triad. His 57 removes a proton from Ser 195 as the latter nucleophilically attacks the peptide carbonyl to give a tetrahedral intermediate which is stabilised by the NH groups of Gly 193 and Ser 195. Breakdown of the intermediate with protonation of the departing amine by His 57 generates a covalent acyl-enzyme intermediate. This is then hydrolysed using a water molecule that is deprotonated by His 57. Asp 102 functions to modify the pKa of His 57, enabling it to deprotonate Ser 195 and water.
Reaction

Catalytic Sites for 1ssx

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA102262macie:sideChainModifies the pKa of His 57.
SerA195342macie:sideChainActs as a nucleophile to attack the peptide bond carbonyl. Its backbone NH forms part of the oxyanion hole which stabilises the tetrahedral intermediate.
SerA195342macie:mainChainAmideActs as a nucleophile to attack the peptide bond carbonyl. Its backbone NH forms part of the oxyanion hole which stabilises the tetrahedral intermediate.
GlyA193340macie:mainChainAmideForms part of the oxyanion hole that stabilises the tetrahedral intermediate.
HisA57235macie:sideChainRemoves proton from Ser 195 as the Ser 195 acts as a nucleophile to attack the peptide carbonyl. Acts as a general acid to protonate the departing amine leaving group. Later deprotonates a water molecule for nucleophilic attack on the acyl-enzyme intermediate.
SerA214358macie:mainChainCarbonylBackbone carbonyl forms a weak C-H...O hydrogen bond to C-epsilon1 of His 57. This is proposed to help delocalise the charge of the histidine ring, weakening the epsilon2N-H bond and promoting breakdown of the tetrahedral intermediate to the acyl enzyme.

Literature References

Notes:
Fuhrmann CN
The 0.83 A resolution crystal structure of alpha-lytic protease reveals the detailed structure of the active site and identifies a source of conformational strain.
J Mol Biol 2004 338 999-1013
PubMed: 15111063
Sauter NK
Structure of alpha-lytic protease complexed with its pro region.
Nat Struct Biol 1998 5 945-950
PubMed: 9808037
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